Structural characterization of Zika virus proteins and search for antiviral agents

Abstract

The Zika Fever, caused by the Zika Virus (ZIKV), is an emerging disease that in 2016 reached all five continents, achieving the status of a pandemic disease. It not only causes Dengue-like symptoms, the ZIKV can also affect the fetus developing during pregnancy, as well as cause neurological problems in adults, such as the Guillain-Barré Syndrome. Despite the global efforts so far, the mechanism of transmission, replication, immune evasion and also possible negative effects caused by the ZIKV are not fully understood. So far, there are no treatments or efficient ways of eradicating the virus, and prevention and control of the mosquito are the only way of fighting the ZIKV. The ZIKV is a positive chain retrovirus, where its genetic material translates a single poliprotein that is cleaved into ten different proteins. Of those, two form the viral envelope, one the capsid, and seven are involved in the virus replication. The proteins of the envelope and the NS1-ladder-domain, NS3-protease and NS5-methyltransferase have had parts of their tridimensional structures solved. Our proposal is to study the not yet solved proteins of ZIKV, by using biomolecular and X-ray crystallography techniques, aiming the structural determination of those. Once determined, the tridimensional structures will be used for the study of ligands with antiviral applicability. This project is part of the CEPID CIBFar from FAPESP, and has a secondary goal of establishing the necessary bases for the study of viruses in our lab. (AU)